Relative costs of new water supply options for Front Range cities: phase 2 report

June 2011.Prepared for the Colorado Water Conservation Board and the Colorado Water Institute.Published as part of the Western Water Policy Program at the University of Colorado's Natural Resources Law Center.Includes bibliographical references.The following report is the second (and final) installment of a project examining the costs associated with meeting future M&I (municipal and industrial) water supplies along Colorado's Front Range. As summarized in the recently updated Statewide Water Supply Initiative (SWSI 2010) reports, M&I water demand in Colorado is expected to climb by 600,000 to one million AF (AF) by 2050 (CWCB, 2010). Some mixture of three strategies will likely be necessary to meet this target: new water projects, water transfers (i.e., agricultural to urban reallocation), and conservation. Determining which option(s) is "best" is a complex matter that requires weighing highly case-specific opportunities, constraints, trade-offs, risks, uncertainties, and values. Presumably, among the most important considerations is economic cost. In this Phase 2 report, we continue our consideration of what is known and unknown about the economic costs of meeting these future water demands

The Importance of Audit Firm Characteristics and the Drivers of Auditor Change in UK Listed Companies

This paper explores the importance of audit firm characteristics and the factors motivating auditor change based on questionnaire responses from 210 listed UK companies (a response rate of 70%). Twenty-nine potentially desirable auditor characteristics are identified from the extant literature and their importance elicited. Exploratory factor analysis reduces these variables to eight uncorrelated underlying dimensions: reputation/quality; acceptability to third parties; value for money; ability to provide non-audit services; small audit firm; specialist industry knowledge; non-Big Six large audit firm; and geographical proximity. Insights into the nature of 'the Big Six factor' emerge. Two thirds of companies had recently considered changing auditors; the main reasons cited being audit fee level, dissatisfaction with audit quality and changes in top management. Of those companies that considered change, 73% did not actually do so, the main reasons cited being fee reduction by the incumbent and avoidance of disruption. Thus audit fee levels are both a key precipitator of change and a key factor in retaining the status quo

iSAW: Integrating Structure, Actors, and Water to Study Socio-Hydro-Ecological Systems

Urbanization, climate, and ecosystem change represent major challenges for managing water resources. Although water systems are complex, a need exists for a generalized representation of these systems to identify important components and linkages to guide scientific inquiry and aid water management. We developed an integrated Structure-Actor-Water framework (iSAW) to facilitate the understanding of and transitions to sustainable water systems. Our goal was to produce an interdisciplinary framework for water resources research that could address management challenges across scales (e.g., plot to region) and domains (e.g., water supply and quality, transitioning, and urban landscapes). The framework was designed to be generalizable across all human–environment systems, yet with sufficient detail and flexibility to be customized to specific cases. iSAW includes three major components: structure (natural, built, and social), actors (individual and organizational), and water (quality and quantity). Key linkages among these components include: (1) ecological/hydrologic processes, (2) ecosystem/geomorphic feedbacks, (3) planning, design, and policy, (4) perceptions, information, and experience, (5) resource access and risk, and (6) operational water use and management. We illustrate the flexibility and utility of the iSAW framework by applying it to two research and management problems: understanding urban water supply and demand in a changing climate and expanding use of green storm water infrastructure in a semi-arid environment. The applications demonstrate that a generalized conceptual model can identify important components and linkages in complex and diverse water systems and facilitate communication about those systems among researchers from diverse disciplines

Synaptic Neurotransmission Depression in Ventral Tegmental Dopamine Neurons and Cannabinoid-Associated Addictive Learning

Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction

FŒTAL RESPIRATION.

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2-Pyridylquinolone antimalarials with improved antimalarial activity and physicochemical properties

A series of 2-pyridylquinolones has been prepared in 5–7 steps and through lead optimisation, antimalarial activity as low as 12 nM against Plasmodium falciparum (Pf) has been achieved. Compared with previous analogues in this series, selected molecules have improved solubility, a reduced potential for off-target toxicity and improved metabolic stability profiles. Docking studies performed with a homology model of the Pfbc1 complex target demonstrate a key role for the Tyr16 residues in the recognition of highly active quinolone based inhibitor